Ambient temperature and risk of cardiovascular hospitalization: An updated systematic review and meta-analysis

The association between temperatures and risk of cardiovascular mortality has been recognized but the association drawn from previous meta-analysis was weak due to the lack of sufficient studies. This paper presented a review with updated reports in the literature about the risk of cardiovascular hospitalization in relation to different temperature exposures and examined the dose–response relationship of temperature-cardiovascular hospitalization by change in units of temperature, latitudes, and lag days. The pooled effect sizes were calculated for cold, heat, heatwave, and diurnal variation using random-effects meta-analysis, and the dose–response relationship of temperature-cardiovascular admission was modelled using random-effect meta-regression. The Cochrane Q-test and index of heterogeneity (I2) were used to evaluate heterogeneity, and Egger's test was used to evaluate publication bias. Sixty-four studies were included in meta-analysis. The pooled results suggest that for a change in temperature condition, the risk of cardiovascular hospitalization increased 2.8% (RR, 1.028; 95% CI, 1.021–1.035) for cold exposure, 2.2% (RR, 1.022; 95% CI, 1.006–1.039) for heatwave exposure, and 0.7% (RR, 1.007; 95% CI, 1.002–1.012) for an increase in diurnal temperature. However no association was observed for heat exposure. The significant dose–response relationship of temperature — cardiovascular admission was found with cold exposure and diurnal temperature. Increase in one-day lag caused a marginal reduction in risk of cardiovascular hospitalizations for cold exposure and diurnal variation, and increase in latitude was associated with a decrease in risk of cardiovascular hospitalizations for diurnal temperature only. There is a significant short-term effect of cold exposure, heatwave and diurnal variation on cardiovascular hospitalizations. Further research is needed to understand the temperature-cardiovascular relationship for different climate areas.

Crystal structure of ferroelectric sodium meta vanadate, NaVO3

The crystal structure of ferroelectric sodium meta vanadate, NaVO3 has been solved using three dimensional X-ray data and refined to an R-value of 0.077 for 375 observed reflections. The crystal belongs to the monoclinic system with space group Cc and with unit cell dimensions a = 10.494 (9) Aring, b = 9.434 (7) Aring, c = 5.863 (6) Aring and β = 108° 48' in the room temperature ferroelectric phase. The unit cell dimensions in the high temperature paraelectric phase (above 380°C) are a = 10.595 (15) Aring, b = 9.671 (10) Aring, c = 5.926 (8) Aring and β = 108° 45' with space group C2/c. The crystal structure may be viewed as consisting of alternate channels of sodium polyhedra and VO4 tetrahedra.

Family-based interventions in preventing children and adolescents from using tobacco: A systematic review and meta-analysis

- Background Tobacco is the main preventable cause of death and disease worldwide. Adolescent smoking is increasing in many countries with poorer countries following the earlier experiences of affluent countries. Preventing adolescents starting smoking is crucial to decreasing tobacco-related illness. - Objective To assess effectiveness of family-based interventions alone and combined with school-based interventions to prevent children and adolescents from initiating tobacco use. - Data Sources 14 bibliographic databases and the Internet, journals hand-searched, experts consulted. - Study Eligibility Criteria, Participants, and Interventions Randomised controlled trials (RCTs) with children or adolescents and families, interventions to prevent starting tobacco use, follow-up ≥ 6 months. - Study Appraisal/Synthesis methods Abstracts/titles independently assessed and data independently entered by two authors. Risk-of-bias assessed with the Cochrane Risk-of-Bias tool. - Results Twenty-seven RCTs were included. Nine trials of never-smokers compared to a control provided data for meta-analysis. Family intervention trials had significantly fewer students who started smoking. Meta-analysis of twoRCTs of combined family and school interventions compared to school only, showed additional significant benefit. The common feature of effective high intensity interventions was encouraging authoritative parenting. - Limitations Only 14 RCTs provided data for meta-analysis (about 1/3 of participants). Of the 13 RCTs which did not provide data for meta-analysis eight compared a family intervention to no intervention and one found significant effects, and five compared a family + school intervention to a school intervention and none found additional significant effects. - Conclusions and Implications of Key Findings There is moderate quality evidence that family-based interventions prevent children and adolescents starting to smoke.

Ecological impacts of Phlebiopsis gigantea biocontrol treatment against Heterobasidion spp. as revealed by fungal community profiling and population analyses

Wood decay fungi belonging to the species complex Heterobasidion annosum sensu lato are among the most common and economically important species causing root rot and stem decay in conifers of the northern temperate regions. New infections by these pathogens can be suppressed by tree stump treatments using chemical or biological control agents. In Finland, the corticiaceous fungus Phlebiopsis gigantea has been formulated into a commercial biocontrol agent called Rotstop (Verdera Ltd.). This thesis addresses the ecological impacts of Rotstop biocontrol treatment on the mycoflora of conifer stumps. Locally, fungal communities within Rotstop-treated and untreated stumps were analyzed using a novel method based on DGGE profiling of small subunit ribosomal DNA fragments amplified directly from wood samples. Population analyses for P. gigantea and H. annosum s.l. were conducted to evaluate possible risks associated with local and/or global distribution of the Rotstop strain. Based on molecular community profiling by DGGE, we detected a few individual wood-inhabiting fungal species (OTUs) that seemed to have suffered or benefited from the Rotstop biocontrol treatment. The DGGE analyses also revealed fungal diversity not retrieved by cultivation and some fungal sequence types untypical for decomposing conifer wood. However, statistical analysis of DGGE community profiles obtained from Rotstop-treated and untreated conifer stumps revealed that the Rotstop treatment had not caused a statistically significant reduction in the species diversity of wood-inhabiting fungi within our experimental forest plots. Locally, ISSR genotyping of cultured P. gigantea strains showed that the Rotstop biocontrol strain was capable of surviving up to six years within treated Norway spruce stumps, while in Scots pine stumps it was sooner replaced by successor fungal species. In addition, the spread of resident P. gigantea strains into Rotstop-treated forest stands seemed effective in preventing the formation of genetically monomorphic populations in the short run. On a global scale, we detected a considerable level of genetic differentiation between the interfertile European and North American populations of P. gigantea. These results strongly suggest that local biocontrol strains should be used in order to prevent global spread of P. gigantea and hybrid formation between geographically isolated populations. The population analysis for H. annosum s.l. revealed a collection of Chinese fungal strains that showed a high degree of laboratory fertility with three different allopatric H. annosum s.l. taxa. However, based on the molecular markers, the Chinese strains could be clearly affiliated with the H. parviporum taxonomical cluster, which thus appears to have a continuous distribution range from Europe through southern Siberia to northern China. Keywords: Rotstop, wood decay, DGGE, ISSR fingerprinting, ribosomal DNA

Polyvanadate-stimulated NADH oxidation by plasma membranes-The need for a mixture of deca and meta forms of vanadate

Polyvanadate solutions obtained by extracting vanadium pentoxide with dilute alkali over a period of several hours contained increasing amounts of decavanadate as characterized by NMR and ir spectra. Those solutions having a metavanadate:decavanadate ratio in the range of 1-5 showed maximum stimulation of NADH oxidation by rat liver plasma membranes. Reduction of decavanadate, but not metavanadate, was obtained only in the presence of the plasma membrane enzyme system. High simulation of activity of NADH oxidation was obtained with a mixture of the two forms of vanadate and this further increased on lowering the pH. Addition of increasing concentrations of decavanadate to metavanadate and vice versa increased the stimulatory activity, reaching a maximum when the metavanadate:decavanadate ratio was in the range of 1-5. Increased stimulatory activity can also be obtained by reaching these ratios by conversion of decavanadate to metavanadate by alkaline phosphate degradation, and of metavanadate to decavanadate by acidification. These studies show for the first time that both deca and meta forms of vanadate present in polyvanadate solutions are needed for maximum activity of NADH oxidation.

Platelet endothelial cell adhesion molecule 1 (PECAM-1) and its interactions with glycosaminoglycans: 2. Biochemical analyses

Platelet endothelial cell adhesion molecule 1 (PECAM-1) (CD31), a member of the immunoglobulin (Ig) superfamily of cell adhesion molecules with six Ig-like domains, has a range of functions, notably its contributions to leukocyte extravasation during inflammation and in maintaining vascular endothelial integrity. Although PECAM-1 is known to mediate cell adhesion by homophilic binding via domain 1, a number of PECAM-1 heterophilic ligands have been proposed. Here, the possibility that heparin and heparan sulfate (HS) are ligands for PECAM-1 was reinvestigated. The extracellular domain of PECAM-1 was expressed first as a fusion protein with the Fc region of human IgG1 fused to domain 6 and second with an N-terminal Flag tag on domain 1 (Flag-PECAM-1). Both proteins bound heparin immobilized on a biosensor chip in surface plasmon resonance (SPR) binding experiments. Binding was pH-sensitive but is easily measured at slightly acidic pH. A series of PECAM-1 domain deletions, prepared in both expression systems, were tested for heparin binding. This revealed that the main heparin-binding site required both domains 2 and 3. Flag-PECAM-1 and a Flag protein containing domains 1-3 bound HS on melanoma cell surfaces, but a Flag protein containing domains 1-2 did not. Heparin oligosaccharides inhibited Flag-PECAM-1 from binding immobilized heparin, with certain structures having greater inhibitory activity than others. Molecular modeling similarly identified the junction of domains 2 and 3 as the heparin-binding site and further revealed the importance of the iduronic acid conformation for binding. PECAM-1 does bind heparin/HS but by a site that is distinct from that required for homophilic binding.

Computational analyses of the catalytic and heparin-binding sites and their interactions with glycosaminoglycans in glycoside hydrolase family 79 endo-d-glucuronidase (heparanase)

Mammalian heparanase is an endo-β-glucuronidase associated with cell invasion in cancer metastasis, angiogenesis and inflammation. Heparanase cleaves heparan sulfate proteoglycans in the extracellular matrix and basement membrane, releasing heparin/heparan sulfate oligosaccharides of appreciable size. This in turn causes the release of growth factors, which accelerate tumor growth and metastasis. Heparanase has two glycosaminoglycan-binding domains; however, no three-dimensional structure information is available for human heparanase that can provide insights into how the two domains interact to degrade heparin fragments. We have constructed a new homology model of heparanase that takes into account the most recent structural and bioinformatics data available. Heparin analogs and glycosaminoglycan mimetics were computationally docked into the active site with energetically stable ring conformations and their interaction energies were compared. The resulting docked structures were used to propose a model for substrates and conformer selectivity based on the dimensions of the active site. The docking of substrates and inhibitors indicates the existence of a large binding site extending at least two saccharide units beyond the cleavage site (toward the nonreducing end) and at least three saccharides toward the reducing end (toward heparin-binding site 2). The docking of substrates suggests that heparanase recognizes the N-sulfated and O-sulfated glucosamines at subsite +1 and glucuronic acid at the cleavage site, whereas in the absence of 6-O-sulfation in glucosamine, glucuronic acid is docked at subsite +2. These findings will help us to focus on the rational design of heparanase-inhibiting molecules for anticancer drug development by targeting the two heparin/heparan sulfate recognition domains.

Microarrays in Lung Cancer Research: From Comparative Analyses to Verified Findings

Keuhkosyöpä on yleisimpiä syöpätauteja. Se jaetaan kahteen päätyyppiin: pienisoluiseen ja ei-pienisoluiseen keuhkosyöpään. Ei-pienisoluinen keuhkosyöpä jaetaan lisäksi alatyyppeihin, joista suurimmat ovat levyepiteeli-, adeno- ja suurisoluinen karsinooma. Keuhkosyövän tärkein riskitekijä on tupakointi, mutta muutkin työ- ja elinympäristön altisteet, kuten asbesti, voivat johtaa syöpään. Väitöstyössä tutkittiin kahdenlaisten keuhkosyöpäryhmien erityispiirteitä. Työssä kartoitettiin, onko löydettävissä muutoksia, jotka erottavat asbestikeuhkosyövät muista syövistä sekä luuytimeen varhaisessa vaiheessa leviävät keuhkosyövät leviämättömistä syövistä. Tutkimusten ensimmäisessä vaiheessa käytettiin mikrosirupohjaisia menetelmiä, jotka mahdollistavat jopa kaikkien geenien tarkastelun yhden kokeen avulla. Vertailevien mikrosirututkimusten avulla on mahdollista paikantaa geenejä tai kromosomialueita, joiden muutokset erottelevat ryhmät toisistaan. Asbestiin liittyvissä tutkimuksissa paikannettiin kuusi kromosomialuetta, joissa geenien kopiolukumäärän sekä ilmenemistason muutokset erottelivat potilaat altistushistorian mukaan. Riippumattomilla laboratoriomenetelmillä tehtyjen jatkoanalyysien avulla pystyttiin varmistamaan, että 19p-alueen häviämä oli yhteydessä asbestialtistukseen. Työssä osoitettiin myös, että 19p-alueen muutoksia voidaan indusoida altistamalla soluja asbestille in vitro. Tutkimuksessa saatiin lisäksi viitteitä asbestispesifisistä muutoksista signaalinvälitysreiteissä, sillä yhdessä toimivien geenien ilmentymisessä havaittiin eroja asbestille altistuneiden ja altistumattomien välillä. Vertailemalla luuytimeen syövän aikaisessa vaiheessa levinneiden ja leviämättömien keuhkoadenokarsinoomien muutosprofiileita toisiinsa, paikannettiin viisi aluetta, joilla geenien kopiolukumäärä- sekä ilmenemistason muutokset erottelivat ryhmät toisistaan. Jatkoanalyyseissä havaittiin, että 4q-alueen häviämää esiintyi adenokarsinoomien lisäksi levyepiteelikarsinoomiin, jotka olivat levinneet luuytimeen. Myös keuhkosyöpien aivometastaaseissa alue oli toistuvasti hävinnyt. Väitöstyön tutkimukset osoittavat, että vertailevien mikrosiruanalyysien avulla saadaan tietoa syöpäryhmien erityispiirteistä. Työssä saadut tulokset osoittavat, että 19p-alueen muutokset ovat tyypillisiä asbestikeuhkosyöville ja 4q-alueen muutokset luuytimeen aikaisessa vaiheessa leviäville keuhkosyöville.

Crystal structures and thermal analyses of alkyl 2-deoxy-alpha-D-arabino-hexopyranosides

The crystal structures of alkyl 2-deoxy-alpha-D-arabino-hexopyranosides, with the alkyl chain lengths from C-8 to C-18, are established by the single crystal X-ray structural determination. The even-alkyl chain length derivatives crystallized orthorhombic, with space group P2(1)2(1)2(1), whereas the odd-alkyl chain length derivatives crystallized monoclinic, with space group P2(1). The sugar moieties retained a C-4(1) chair conformation and the conformation of the alkyl chains was all-trans. The molecules formed a bilayer structure, in which alkyl chains were interdigitated.The hydrogen bonds, originating from the sugar moieties, were observed in adjacent layers and also within the same layer, resulting in the formation of infinite chains. The alkyl chains arranged parallel to each other and formed planar structures. The thermal properties of the alkyl 2-deoxy glucosides were analyzed further. It was observed that none of the derivatives exhibited mesomorphism. This study establishes that the absence of the hydroxyl group at C-2 of the sugar moiety results in a non-mesogenic nature of the alkyl 2-deoxy-alpha-D-glycosides, as opposed to the profound mesogenic nature of the normal alkyl glycosides.

Laboratory analyses for evaluation of platelet disorders and platelet concentrates

High quality of platelet analytics requires specialized knowledge and skills. It was applied to analyze platelet activation and aggregation responses in a prospective controlled study of patients with Finnish type of amyloidosis. The 20 patients with AGel amyloidosis displayed a delayed and more profound platelet shape change than healthy siblings and healthy volunteers, which may be related to altered fragmentation of mutated gelsolin during platelet activation. Alterations in platelet shape change have not been reported in association with platelet disorders. In the rare Bernard-Soulier syndrome with Asn45Ser mutation of glycoprotein (GP) IX, the diagnostic defect in the expression of GPIb-IX-V complex was characterized in seven Finnish patients, also an internationally exceptionally large patient series. When measuring thrombopoietin in serial samples of amniotic fluid and cord blood of 15 pregnant women with confirmed or suspected fetal alloimmune thrombocytopenia, the lower limit of detection could be extended. The results approved that thrombopoietin is present already in amniotic fluid. The application of various non-invasive means for diagnosing thrombocytopenia (TP) revealed that techniques for estimating the proportion of young, i.e. large platelets, such as direct measurement of reticulated platelets and the mean platelet size, would be useful for evaluating platelet kinetics in a given patient. Due to different kinetics between thrombopoietin and increase of young platelets in circulation, these measurements may have most predictive value when measured from simultaneous samples. Platelet autoantibodies were present not only in isolated autoimmune TP but also in patients without TP where disappearance of platelets might be compensated by increased production. The autoantibodies may also persist after TP has been cured. Simultaneous demonstration of increased young platelets (or increased mean platelet volume) in peripheral blood and the presence of platelet associated IgG specificities to major glycoproteins (GPIb-IX and GPIIb-IIIa) may be considered diagnostic for autoimmune TP. Measurement of a soluble marker as a sign of thrombin activation and proceeding deterioration of platelet components was applied to analyze the alterations under several stress factors (storage, transportation and lack of continuous shaking under controlled conditions) of platelet products. The GPV measured as a soluble factor in platelet storage medium showed good correlation with an array of other measurements commonly applied in characterization of stored platelets. The benefits of measuring soluble analyte in a quantitative assay were evident.

Prevalence of foot disease and risk factors in general inpatient populations: A systematic review and meta-analysis

Objective: To systematically review studies reporting the prevalence in general adult inpatient populations of foot disease disorders (foot wounds, foot infections, collective ‘foot disease’) and risk factors (peripheral arterial disease (PAD), peripheral neuropathy (PN), foot deformity). Methods: A systematic review of studies published between 1980 and 2013 was undertaken using electronic databases (MEDLINE, EMBASE and CINAHL). Keywords and synonyms relating to prevalence, inpatients, foot disease disorders and risk factors were used. Studies reporting foot disease or risk factor prevalence data in general inpatient populations were included. Included study's reference lists and citations were searched and experts consulted to identify additional relevant studies. 2 authors, blinded to each other, assessed the methodological quality of included studies. Applicable data were extracted by 1 author and checked by a second author. Prevalence proportions and SEs were calculated for all included studies. Pooled prevalence estimates were calculated using random-effects models where 3 eligible studies were available. Results: Of the 4972 studies initially identified, 78 studies reporting 84 different cohorts (total 60 231 517 participants) were included. Foot disease prevalence included: foot wounds 0.01–13.5% (70 cohorts), foot infections 0.05–6.4% (7 cohorts), collective foot disease 0.2–11.9% (12 cohorts). Risk factor prevalence included: PAD 0.01–36.0% (10 cohorts), PN 0.003–2.8% (6 cohorts), foot deformity was not reported. Pooled prevalence estimates were only able to be calculated for pressure ulcer-related foot wounds 4.6% (95% CI 3.7% to 5.4%)), diabetes-related foot wounds 2.4% (1.5% to 3.4%), diabetes-related foot infections 3.4% (0.2% to 6.5%), diabetes-related foot disease 4.7% (0.3% to 9.2%). Heterogeneity was high in all pooled estimates (I2=94.2–97.8%, p<0.001). Conclusions: This review found high heterogeneity, yet suggests foot disease was present in 1 in every 20 inpatients and a major risk factor in 1 in 3 inpatients. These findings are likely an underestimate and more robust studies are required to provide more precise estimates.

The influence of OLR1 and PCSK9 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis

It has been reported that both OLR1 and PCSK9 genes are related to various vascular diseases such as atherosclerosis, cardiovascular disease, peripheral artery disease and stroke, in particular ischemic stroke. The prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between OLR1 rs11053646 and PCSK9 rs505151 polymorphisms and the risk of ischemic stroke remains unclear and inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of genetic polymorphisms on ischemic stroke, by analyzing the complete coverage of all relevant studies. All eligible case-control and cohort studies that met the search term were retrieved in multiple scientific databases. Data of interest such as demographic data and genotyping methods were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. A total of seven case-control studies encompassing 1897 ischemic stroke cases and 2119 healthy controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR=1.33. 95%CI:1.11-1.58) and co-dominant models (OR=1.24, 95%CI:1.02-1.51) were significantly associated with ischemic stroke. For PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR=1.36, 95%CI:1.01-1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G>C and PCSK9 rs505151 A>G may contribute to the susceptibility risk of ischemic stroke.

Improved procedures for static and dynamic analyses of wrinkled membranes

An analysis of large deformations of flexible membrane structures within the tension field theory is considered. A modification-of the finite element procedure by Roddeman et al. (Roddeman, D. G., Drukker J., Oomens, C. W J., Janssen, J. D., 1987, ASME J. Appl. Mech. 54, pp. 884-892) is proposed to study the wrinkling behavior of a membrane element. The state of stress in the element is determined through a modified deformation gradient corresponding to a fictive nonwrinkled surface. The new model uses a continuously modified deformation gradient to capture the location orientation of wrinkles more precisely. It is argued that the fictive nonwrinkled surface may be looked upon as an everywhere-taut surface in the limit as the minor (tensile) principal stresses over the wrinkled portions go to zero. Accordingly, the modified deformation gradient is thought of as the limit of a sequence of everywhere-differentiable tensors. Under dynamic excitations, the governing equations are weakly projected to arrive at a system of nonlinear ordinary differential equations that is solved using different integration schemes. It is concluded that, implicit integrators work much better than explicit ones in the present context.